4URK

PI3Kg in complex with AZD6482

Summary for 4URK

• Entry DOI: 10.2210/pdb4urk/pdb
• Descriptor: PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT GAMMA ISOFORM, 2-[[(1R)-1-(7-methyl-2-morpholin-4-yl-4-oxidanylidene-pyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoic acid (2 entities in total)
• Functional Keywords: transferase, lipid kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P48736
• Total number of polymer chains: 1
• Total formula weight: 111135.55

Authors

Giordanetto, F.,Barlaam, B.,Berglund, S.,Edman, K.,Karlsson, O.,Lindberg, J.,Nylander, S.,Inghardt, T. (deposition date: 2014-06-30, release date: 2014-10-22, Last modification date: 2024-01-10)

Primary citation

Giordanetto, F.,Barlaam, B.,Berglund, S.,Edman, K.,Karlsson, O.,Lindberg, J.,Nylander, S.,Inghardt, T.
Discovery of 9-(1-Phenoxyethyl)-2-Morpholino-4-Oxo-Pyrido[1, 2-A]Pyrimidine-7-Carboxamides as Oral Pi3Kbeta Inhibitors, Useful as Antiplatelet Agents.
Bioorg.Med.Chem.Lett., 24:3936-, 2014

PubMed Abstract: Optimization of AZD6482 (2), the first antiplatelet PI3Kβ inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kβ inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.

PubMed: 25042253
DOI: 10.1016/J.BMCL.2014.07.007

Experimental method

X-RAY DIFFRACTION (2.9 Å)